Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis

Necroptosis is a form of regulated cell death that has been implicated in multiple diseases. TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL. In this study, by screening of a small-compound library, we identified dozens of compounds that inhibited TN...

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Autores principales: Huang, Fangmin, Liang, Jiankun, Lin, Yingying, Chen, Yushi, Hu, Fen, Feng, Jianting, Zeng, Qiang, Han, Zeteng, Lin, Qiaofa, Li, Yan, Li, Jingyi, Wu, Lanqin, Li, Lisheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517925/
https://www.ncbi.nlm.nih.gov/pubmed/37741898
http://dx.doi.org/10.1038/s42003-023-05353-5
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author Huang, Fangmin
Liang, Jiankun
Lin, Yingying
Chen, Yushi
Hu, Fen
Feng, Jianting
Zeng, Qiang
Han, Zeteng
Lin, Qiaofa
Li, Yan
Li, Jingyi
Wu, Lanqin
Li, Lisheng
author_facet Huang, Fangmin
Liang, Jiankun
Lin, Yingying
Chen, Yushi
Hu, Fen
Feng, Jianting
Zeng, Qiang
Han, Zeteng
Lin, Qiaofa
Li, Yan
Li, Jingyi
Wu, Lanqin
Li, Lisheng
author_sort Huang, Fangmin
collection PubMed
description Necroptosis is a form of regulated cell death that has been implicated in multiple diseases. TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL. In this study, by screening of a small-compound library, we identified dozens of compounds that inhibited TNF-induced necroptosis. According to the mechanisms by which they inhibited necroptosis, these compounds were classified into different groups. We then identified Ibrutinib as an inhibitor of RIPK3 and found that Quizartinib protected against the TNF-induced systemic inflammatory response syndrome in mice by inhibiting the activation of RIPK1. Altogether, our work revealed dozens of necroptosis inhibitors, suggesting new potential approaches for treating necroptosis-related diseases.
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spelling pubmed-105179252023-09-25 Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis Huang, Fangmin Liang, Jiankun Lin, Yingying Chen, Yushi Hu, Fen Feng, Jianting Zeng, Qiang Han, Zeteng Lin, Qiaofa Li, Yan Li, Jingyi Wu, Lanqin Li, Lisheng Commun Biol Article Necroptosis is a form of regulated cell death that has been implicated in multiple diseases. TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL. In this study, by screening of a small-compound library, we identified dozens of compounds that inhibited TNF-induced necroptosis. According to the mechanisms by which they inhibited necroptosis, these compounds were classified into different groups. We then identified Ibrutinib as an inhibitor of RIPK3 and found that Quizartinib protected against the TNF-induced systemic inflammatory response syndrome in mice by inhibiting the activation of RIPK1. Altogether, our work revealed dozens of necroptosis inhibitors, suggesting new potential approaches for treating necroptosis-related diseases. Nature Publishing Group UK 2023-09-23 /pmc/articles/PMC10517925/ /pubmed/37741898 http://dx.doi.org/10.1038/s42003-023-05353-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Huang, Fangmin
Liang, Jiankun
Lin, Yingying
Chen, Yushi
Hu, Fen
Feng, Jianting
Zeng, Qiang
Han, Zeteng
Lin, Qiaofa
Li, Yan
Li, Jingyi
Wu, Lanqin
Li, Lisheng
Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis
title Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis
title_full Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis
title_fullStr Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis
title_full_unstemmed Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis
title_short Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis
title_sort repurposing of ibrutinib and quizartinib as potent inhibitors of necroptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517925/
https://www.ncbi.nlm.nih.gov/pubmed/37741898
http://dx.doi.org/10.1038/s42003-023-05353-5
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